The receptors and actions of the hypothalamic releasing peptides, GnRH and CRF, have been characterized in the pituitary gland, and current studies are directed at the clarification of the mechanisms of action of these peptide upon hormone secretion in cultured pituitary cells. The up-regulation of GnRH receptors by GnRH agonists was formed to be preceded by a phase of receptor loss attributable to internalization of the hormone-receptor complex, to be prevented by inhibition of protein synthesis, and to be independent of receptor recruitment to the cell membrane during the acute phase of gonadotropin release from secretory granules. Stimulation of LH release by high potassium was not preceded by receptor loss prior to up-regulation, and a GnRH antagonist caused no change in receptors, indicating the need for agonist-receptor interaction in the initiation of receptor endocytosis and processing. In studies on the role of phospholipid turnover in GnRH action, the ability of phosphatidic acid (PA) to simulate gonadotroph responses elicited by GnRh suggested that PA may participate in the actions of GnRH agonists upon LH release. The previous finding that arachidonic acid and 5-HETE stimulated LH release and could also be involved in the actions of GnRH was extended by analysis of the metabolism of arachidonic acid, and the demonstration that lipoxygenated derivatives are produced in purified rat gonadotrophs. The potential role of protein kinase C in GnRH action was indicated by its presence in the pituitary gland and the ability of phorbol esters ot activate LH secretion. Studies were commenced in the binding of GnRH in the rat brain, to localize the central sites of which GnRH receptors participate in the behavioral and other CNS actions of GnRH-related peptides. The receptors for CRF in the pituitary gland was also further analyzed during the down-regulation that follows adrenalectomy, and studies on brain CRF receptors were initiated by the technique of topical autoradiography with radioidinated Tyr-oCRF. The properties, regulation, and activation mechanisms of brain CRF receptors will be compared with those of the anterior pituitary gland.